The ability of growth hormone (GH) to have both positive and negative actions on carbohydrate metabolism is well established. The latter includes the production of hyperglycemia and glucose intolerance in both animals and humans. The strong correlation between the glycemic state of the individual and the risk for retinopathy and other microangiopathies, coupled with recent evidence suggesting a direct action of GH in the development of such complications, emphasize the need to define the role of GH in the development and/or progression of diabetic microangiopathy. Because of the species-specificity related limitations on the availability of human GH for clinical use, this problem has been restricted to a relatively small group of patients. With the advent of new technology for biosynthetic production of large amounts of the hormone, the probability of increased incidence and clinical impact of this action of GH is becoming apparent. The objective of this project is to initiate studies to define this role and one of the possible mechanisms involved, by examining the actions of GH on basement membrane (BM) synthesis in the isolated lens system. These studies represent the initial step toward the long-term objective of clarifying the mechanisms underlying the microvascular complications in various organ systems in diabetics and the hormonal influences on these processes. The synthesis and processing of BM by lens epithelial cells will be assessed in lenses isolated from groups of animals which vary in circulating glucose and hormone status. These modifications will be accomplished by hypophysectomy, implantation of GH-secreting tumors, interference with pancreatic insulin secretion (streptozotocin), and/or administration of exogenous substances. The direct effects of substances (glucose, GH, IGF, insulin) on lens cell metabolism will be assessd by in vitro techniques. Standard biochemical methods will be used to detect changes in lens cell metabolism and BM composition. Successful demonstration of changes in BM synthesis which correlate with exposure to GH, alone or in combination with other substances, would indicate the feasibility of this approach and provide the rationale and impetus for definitive studies of the role of GH in the development and progression of the secondary complications (retinopathy, nephropathy, neuropathy) of diabetes. Thus, the approach will provide clues about the pathogenesis of microangiopathy, indicate the potential complications related to GH-therapy and suggest possible ways to minimize the risk of both.